The object of this research program is to investigate, in a simple controlled system, the factors involved in lipid accumulation. Isolated mammalian cells are used and exposed to test media with known lipid compositions. Combined ultrastructural, histochemical and biochemical procedures are employed in order to correlate lipid accumulation with structural alterations and functional abnormalities. Cellular injuries including hypoxia, specific metabolic inhibitors, drugs and agents that increase membrane permeability are being studied to determine their effect on the uptake and accumulation of the different forms of lipid used in the experimental system. Various combinations of injuries are used in order to study additive effects on lipid deposition. Modifications in the environment that tend to limit or reverse lipid accumulation will be examined. The previously noted striking toxic effects of long-chain saturated, as opposed to unsaturated, fats on cell structure and function will be further pursued. The basic objective of this research is to increase our understanding of the pathogenesis and injurious effects of lipid deposition, so that scientific approaches toward control of this process could be developed that would have eventual clinical significance in lipid accumulative disorders such as atherosclerosis.